The long-term objective of this proposal is the prevention of autoimmune mediated Type 1 diabetes mellitus (T1DM). T1DM is a serious life limiting disease that strikes predominantly in children and adolescents. The TrialNet clinical research network, the focus of the proposal, designs and conducts studies aimed at preventing or delaying the onset or progression of type 1 diabetes, both highly relevant public health goals. Many promising interventions must be tested in a safe and efficient manner in order to achieve this goal. A well-organized cooperative network of capable institutes, the Type 1 Diabetes TrialNet group, has greatly facilitated the prompt completion of many clinical trials needed to test these potential interventions. The application responds to the RFA to select the clinical centers that will form TrialNet for the next 5 years. The goal of this proposal is to both continu and improve the infrastructure essential to completing the current TrialNet studies seeking to prevent T1DM in subjects at risk for T1DM, and to preserve endogenous insulin secretion in subjects with new onset T1DM. This application reviews Stanford's five-year experience as a successful and productive TrialNet national center in California and highlights Stanford's plans for extending and improving recruitment and retention activities for the next 5 years. These plans include both completing the current TrialNet studies and implementing the expected upcoming trials. The Stanford University TrialNet Center aggressively recruits relatives into the Pathway to Prevention study both at Stanford University and across our affiliate network in California, Nevada, and Arizona. This study is the path to all of TrialNet's T1DM prevention trials. Our center has been very successful at transitioning eligible subjects into TrialNet's randomized prevention trials. Long-term retention of Stanford's subjects in all studies continues to be outstanding. The Stanford University TrialNet Center has enrolled subjects in four Mechanistic trials, six trials designed to preserve endogenous insulin product at the onset of T1DM, and five T1DM prevention trials. Stanford is particularly proud of its role in conceiving and leading the Effects of Metabolic at Onset of Diabetes on Progression of T1DM to its successful conclusion. The Stanford University TrialNet Center is well positioned to continue to support TrialNet's ultimate raison d'?tre, the prevention of T1DM.